Metabolic regulation of misfolded protein import into mitochondria.
Elife
; 122024 Jun 20.
Article
en En
| MEDLINE
| ID: mdl-38900507
ABSTRACT
Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the 'mitochondria as guardian in cytosol' (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in Saccharomyces cerevisiae uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
/
Pliegue de Proteína
/
Transporte de Proteínas
/
Mitocondrias
Límite:
Humans
Idioma:
En
Revista:
Elife
/
ELife (Cambridge)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos